Blood is a liquid tissue that includes red cells, white cells, corpuscles, and platelets dispersed in a liquid phase. The liquid phase is plasma, which includes acids, lipids, dissolved electrolytes, and proteins. One particular protein suspended in the liquid phase is fibrinogen. When bleeding occurs, the fibrinogen reacts with water and thrombin (an enzyme) to form fibrin, which is insoluble in blood and polymerizes to form clots.
In a wide variety of circumstances, animals, including humans, can suffer from bleeding due to wounds or during surgical procedures. In some circumstances, the bleeding is relatively minor, and normal blood clotting functions in addition to the application of simple first aid are all that is required. In other circumstances substantial bleeding can occur. These situations usually require specialized equipment and materials as well as personnel trained to administer appropriate aid.
In an effort to address the above-described problems, materials have been developed for controlling excessive bleeding. Topical absorbable hemostats (TAHs) are widely used in surgical applications. TAHs encompass products based on various woven or non-woven fabrics or sponges, typically made of at least partially resorbable materials, ranging from natural to synthetic polymers and combinations thereof, including lactide-glycolide based co-polymers such as Polyglactin 910, oxidized cellulose (OC), oxidized regenerated cellulose (ORC), gelatin, collagen, chitin, chitosan, etc. To improve the hemostatic performance, scaffolds based on the above materials can be combined with biologically-derived clotting factors, such as thrombin and/or fibrinogen.
A number of hemostatic formulations are currently available on the market or in development that utilize lyophilized fibrinogen, frequently in combination with lyophilized thrombin, with hemostatic formulations that are applied in the form of dry powder, semi-liquid paste, liquid formulation, or optionally disposed on a supporting scaffold such as bioabsorbable fabric scaffold.
U.S. Pat. No. 7,320,962 entitled “Hemoactive compositions and methods for their manufacture and use”, discloses a dried hemoactive material for inhibiting bleeding or delivering an agent, comprising: a cross-linked biologically compatible polymer which forms a hydrogel when exposed to blood; and a non-cross-linked biologically compatible polymer which solubilizes when exposed to blood: wherein the cross-linked polymer is dispersed in a dried matrix of the non-cross-linked polymer.
U.S. Pat. No. 6,706,690 entitled “Hemoactive compositions and methods for their manufacture and use”, discloses a dried material which forms a hydrogel when exposed to blood, said material comprising: a cross-linked biologically compatible polymer which forms a hydrogel when exposed to blood; a non-cross-linked biologically compatible polymer which dissolves when exposed to blood; a plasticizer present in the non-cross-linked biologically compatible polymer; and wherein the cross-linked polymer is dispersed in a dried matrix of the non-cross-linked polymer, wherein the non-cross-linked biologically compatible polymer dissolves in 15 minutes or less when exposed to blood.
PCT Patent Publication No. WO 1997/028832 A1 entitled “Composition for Sealing Wounds” discloses a hemostatic bandage that contains powdered fibrinogen and thrombin adhered to a fibrous matrix with a viscous, nonaqueous adhesive such as a viscous polysaccharide, glycol, or petroleum jelly. The nonaqueous adhesive does not allow a hydrolytic reaction to occur between the fibrinogen and thrombin until the bandage is moistened by a body fluid, such as blood and teaches that the bandage can be prepared and stored for prolonged periods while retaining hemostatic activity. The reference further teaches a hemostatic wound dressing, comprising: a fibrous matrix suitable for placement as a pad applied over or inserted into an open, bleeding wound; a mixture of intermingled particles of powdered coagulation factors present on the surface of the matrix, the particles being in sufficiently close contact with each other to form a clot when exposed to an aqueous medium at a physiological pH, the particles being adhered to the matrix by a viscous nonaqueous adhesive, having a viscosity of at least 100 centipoise at 20° C., that inhibits a clotting reaction between the intermingled particles until the particles are exposed to an aqueous medium at physiological pH. The reference further discloses a hemostatic wound dressing, comprising: a fibrous matrix suitable for placement as a pad applied over or inserted into an open, bleeding wound; a mixture of intermingled particles of powdered coagulation factors present throughout the matrix, in sufficiently close contact to form a clot when exposed to an aqueous medium at a physiological pH, the particles being adhered to the matrix by a viscous nonaqueous adhesive that inhibits a clotting reaction between the intermingled particles until the particles are exposed to an aqueous medium at physiological pH, wherein the adhesive is selected from the group consisting of a polysaccharide, polyethylene glycol, propylene glycol, glycerol, and petroleum jelly, which adhesive has been applied to the matrix in a liquid form comprising less than 3% by weight water.
U.S. Patent Publication 2012/0177718 A1 entitled “Wound-Covering Material”, by Chemo Sero Therapeutic Research Institute, discloses a wound-covering material that protects and repairs a wound area caused by an operation, trauma, burn, and the like. The description relates to a wound-covering material comprising thrombin, fibrinogen and a bioabsorbable supporting material. The wound-covering material may further be overlaid with a covering material for retaining moisture. The wound-covering material may consist of a kit of either (1) a bioabsorbable supporting material holding thrombin, and fibrinogen; or (2) a bioabsorbable supporting material holding thrombin, and a bioabsorbable supporting material holding fibrinogen; or (3) thrombin, fibrinogen and a bioabsorbable supporting material. Each of the kits may be combined with a covering material for retaining moisture.
U.S. Patent Publication US2013/0029030 A1 entitled “Method for Promotion of Hemostasis and/or Wound Healing”, by Ferrosan Medical Devices A/S, discloses a matrix material comprising a pharmaceutical composition such as a matrix material with a pharmaceutical composition applied by ultrasonic spray technology on the surface. In one embodiment, the pharmaceutical composition comprises thrombin. The invention further describes a method for making the matrix material which has a pharmaceutical composition coated onto the surface of the matrix material using ultrasonic spray technology. In one specific embodiment, the invention also relates to the use of said matrix material for promotion of hemostasis and/or wound healing. The invention also relates to a kit-of-parts comprising a matrix with a pharmaceutical composition and a container with a peelable lid.